tbuckley/cabot-search huggingface dataset:
Osteopontin characterizes bile duct–associated macrophages and correlates with liver fibrosis severity in primary sclerosing cholangitis
Authors: Kevin De Muynck, Lander Heyerick, Federico F. De Ponti, Bart Vanderborght, Tim Meese, Sanne Van Campenhout, Leen Baudonck, Eva Gijbels, Pedro M. Rodrigues, Jesus M. Banales, Mette Vesterhuus, Trine Folseraas, Charlotte L. Scott, Mathieu Vinken, Malaïka Van der Linden, Anne Hoorens, Jo Van Dorpe, Sander Lefere, Anja Geerts, Filip Van Nieuwerburgh, Xavier Verhelst, Hans Van Vlierberghe, Lindsey Devisscher
Journal: Hepatology (2023)

Background and Aims: Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which pharmacological treatment options are currently unavailable. PSC is strongly associated with colitis and a disruption of the gut-liver axis, and macrophages are involved in the pathogenesis of PSC. However, how gut-liver interactions and specific macrophage populations contribute to PSC is incompletely understood. Approach and Results: We investigated the impact of cholestasis and colitis on the hepatic and colonic microenvironment, and performed an in-depth characterization of hepatic macrophage dynamics and function in models of concomitant cholangitis and colitis. Cholestasis-induced fibrosis was characterized by depletion of resident KCs, and enrichment of monocytes and monocyte-derived macrophages (MoMFs) in the liver. These MoMFs highly express triggering-receptor-expressed-on-myeloid-cells-2 ( Trem2 ) and osteopontin ( Spp1 ), markers assigned to hepatic bile duct-associated macrophages, and were enriched around the portal triad, which was confirmed in human PSC. Colitis induced monocyte/macrophage infiltration in the gut and liver, and enhanced cholestasis-induced MoMF- Trem2 and Spp1 upregulation, yet did not exacerbate liver fibrosis. Bone marrow chimeras showed that knockout of Spp1 in infiltrated MoMFs exacerbates inflammation in vivo and in vitro , while monoclonal antibody–mediated neutralization of SPP1 conferred protection in experimental PSC. In human PSC patients, serum osteopontin levels are elevated compared to control, and significantly increased in advanced stage PSC and might serve as a prognostic biomarker for liver transplant-free survival. Conclusions: Our data shed light on gut-liver axis perturbations and macrophage dynamics and function in PSC and highlight SPP1/OPN as a prognostic marker and future therapeutic target in PSC.
Nonsense-mediated mRNA decay in neuronal physiology and neurodegeneration
Authors: Marija Petrić Howe, Rickie Patani
Journal: Trends in Neurosciences (2023)

The processes of mRNA export from the nucleus and subsequent mRNA translation in the cytoplasm are of particular relevance in eukaryotic cells. In highly polarised cells such as neurons, finely-tuned molecular regulation of these processes serves to safeguard the spatiotemporal fidelity of gene expression. Nonsense-mediated mRNA decay (NMD) is a cytoplasmic translation-dependent quality control process that regulates gene expression in a wide range of scenarios in the nervous system, including neurodevelopment, learning, and memory formation. Moreover, NMD dysregulation has been implicated in a broad range of neurodevelopmental and neurodegenerative disorders. We discuss how NMD and related aspects of mRNA translation regulate key neuronal functions and, in particular, we focus on evidence implicating these processes in the molecular pathogenesis of neurodegeneration. Finally, we discuss the therapeutic potential and challenges of targeting mRNA translation and NMD across the spectrum of largely untreatable neurological diseases.
LINC02159 promotes non-small cell lung cancer progression via ALYREF/YAP1 signaling
Authors: Qiurong Yang, Maoye Wang, Jing Xu, Dan Yu, Yixin Li, Yanke Chen, Xiaoxin Zhang, Jiahui Zhang, Jianmei Gu, Xu Zhang
Journal: Molecular Cancer (2023)

Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have emerged as key regulators of cancer development and progression, and as promising biomarkers for the diagnosis and prognosis of cancer. In this study, we identified a new lncRNA (LINC02159) that was upregulated in the tumor tissues and serum of non-small cell lung cancer (NSCLC) patients. We demonstrated that knockdown of LINC02159 inhibited NSCLC cell proliferation, migration, and invasion, but induced cell apoptosis and cell cycle arrest in vitro and retarded tumor growth in vivo, while overexpression of LINC02159 led to the opposite effect. We discovered that LINC02159 was highly correlated with cancer growth and metastasis-related pathways by using transcriptomic analysis and that YAP1 was a potential target gene of LINC02159. Mechanistically, LINC02159 bound to the Aly/REF export factor (ALYREF) to enhance the stability of YAP1 messenger RNA (mRNA) via m5C modification, which led to the overexpression of YAP1 and the activation of the Hippo and β-catenin signaling pathways in NSCLC cells. Rescue experiments showed that LINC01259 promoted NSCLC progression in a YAP1- and ALYREF-dependent manner. In conclusion, LINC02159 plays an oncogenic role in NSCLC progression by regulating ALYREF/YAP1 signaling, and it has the potential to be utilized as a diagnostic marker and therapeutic target for NSCLC.
Optimal dose and type of physical activity to improve functional capacity and minimise adverse events in acutely hospitalised older adults: a systematic review with dose-response network meta-analysis of randomised controlled trials
Authors: Daniel Gallardo-Gómez, Jesús Del Pozo-Cruz, Hugo Pedder, Rosa M Alfonso-Rosa, Francisco Álvarez-Barbosa, Michael Noetel, Unyime Jasper, Sebastien Chastin, Javier Ramos-Munell, Borja Del Pozo Cruz
Journal: British Journal of Sports Medicine (2023)

To identify the optimal dose and type of physical activity to improve functional capacity and reduce adverse events in acutely hospitalised older adults.Systematic review and Bayesian model-based network meta-analysis.Four databases were searched from inception to 20 June 2022.Randomised controlled trials that assessed the effectiveness of a physical activity-based intervention on at least one functional outcome in people aged ≥50 years hospitalised due to an acute medical condition were included. Pooled effect estimates (ie, standardised mean differences for functional capacity and the ratio of means for adverse events) were calculated using random treatment effects network meta-analysis models.Nineteen studies (3842 participants) met the inclusion criteria. Approximately 100 Metabolic Equivalents of Task per day (METs-min/day) (~40 min/day of light effort or ~25 min/day of moderate effort activities) was the minimal dose to improve the functional capacity of acute hospitalised older adults (standardised mean difference (SMD)=0.28, 95% credible interval (CrI) 0.01 to 0.55). The optimal dose was estimated at 159 METs-min/day (~70 min/day of light effort or ~40 min/day of moderate effort activities; SMD=0.41, 95% CrI 0.08 to 0.72). Ambulation was deemed the most efficient intervention, and the optimal dose was reached at 143 METs-min/day (~50 min/day of slow-paced walking; SMD=0.76, 95% CrI 0.35 to 1.16), showing a high evidential power (87.68%). The minimal effective ambulation dose was estimated at 74 METs-min/day (~25 min/day of slow-paced walking; SMD=0.25, 95% CrI 0.01 to 0.41). Physical activity interventions resulted in a decrease in the rate of adverse events compared with usual care at discharge (ratio of means=0.96, 95% CrI 0.95 to 0.97; median time 7 days).This meta-analysis yielded low to moderate evidence supporting the use of in-hospital supervised physical activity programmes in acutely hospitalised older adults. As little as ~25 min/day of slow-paced walking is sufficient to improve functional capacity and minimise adverse events in this population.PROSPERO CRD42021271999.
Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: report of an investigation
Authors: Carolyn V Gould, Rebecca J Free, Julu Bhatnagar, Raymond A Soto, Tricia L Royer, Warren R Maley, Sean Moss, Matthew A Berk, Rebecca Craig-Schapiro, Rosy Priya L Kodiyanplakkal, Lars F Westblade, Thangamani Muthukumar, Yoram A Puius, Amresh Raina, Azam Hadi, Kymberly A Gyure, Danielle Trief, Marcus Pereira, Matthew J Kuehnert, Vennus Ballen, Debra A Kessler, Kimberly Dailey, Charles Omura, Thuy Doan, Steve Miller, Michael R Wilson, Jennifer A Lehman, Jana M Ritter, Elizabeth Lee, Luciana Silva-Flannery, Sarah Reagan-Steiner, Jason O Velez, Janeen J Laven, Kelly A Fitzpatrick, Amanda Panella, Emily H Davis, Holly R Hughes, Aaron C Brault, Kirsten St George, Amy B Dean, Joel Ackelsberg, Sridhar V Basavaraju, Charles Y Chiu, J Erin Staples, Maria Ajaimy, Yorg Al Azzi, Pallavi Annambhotla, Bryon Backenson, Katherine Belden, Adriana Colovai, Dagan Coppock, Lydia Du, Lindsey Estetter, Marie Le, Roosecelis B. Martines, Matthew Pettengill, Wendy Szymczak, Chairut Vareechon
Journal: The Lancet Microbe (2023)

BackgroundIn 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2–6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients.MethodsFrom Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor.FindingsWe identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation.InterpretationThis investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains.FundingUS Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.
Letter to the Editor: Statement of steatotic liver disease—A great leap toward the global standardization
Authors: Chia-Chi Wang, Yu-Ming Cheng, Jia-Horng Kao
Journal: Hepatology (2023)

1Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taiwan 2Department of Gastroenterology and Hepatology. Tung's Taichung MetroHarbor Hospital 3Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan Authorship statement: Chia-Chi Wang wrote the paper. Yu-Ming Cheng drew the figure. Jia-Horng Kao revises the paper. All authors approved the final version of the manuscript. Correspondence Jia-Horng Kao, Chair Professor, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 100, Taiwan. Email: [email protected]
Thyroid hormone action and liver disease, a complex interplay
Authors: Luigi Marino, Adam Kim, Bin Ni, Francesco S. Celi
Journal: Hepatology (2023)

Thyroid hormone action is involved in virtually all physiological processes. It is well known that the liver and thyroid are intimately linked, with thyroid hormone playing important roles in de novo lipogenesis, beta-oxidation (fatty acid oxidation), cholesterol metabolism, and carbohydrate metabolism. Clinical and mechanistic research studies have shown that thyroid hormone can be involved in chronic liver diseases, including alcohol-associated or NAFLD and HCC. Thyroid hormone action and synthetic thyroid hormone analogs can exert beneficial actions in terms of lowering lipids, preventing chronic liver disease and as liver anticancer agents. More recently, preclinical and clinical studies have indicated that some analogs of thyroid hormone could also play a role in the treatment of liver disease. These synthetic molecules, thyromimetics, can modulate lipid metabolism, particularly in NAFLD/NASH. In this review, we first summarize the thyroid hormone signaling axis in the context of liver biology, then we describe the changes in thyroid hormone signaling in liver disease and how liver diseases affect the thyroid hormone homeostasis, and finally we discuss the use of thyroid hormone-analog for the treatment of liver disease.
“Mighty Casey” Quinlan: outspoken patient activist
Authors: Dave deBronkart, Jan Oldenburg
Journal: BMJ (2023)

Casey Quinlan (b 1952), the patient activist known as "Mighty Casey," died in hospice on 25 April 2023, from a recurrence of metastatic breast cancer.Casey was notorious for having a QR code tattooed on her sternum that linked to her complete medical history online.It was a visible protest against American medicine's inability to give her an integrated record and it was effective activism: it opened eyes and started conversations whenever she appeared at medical conferences.Her video interview tells why she did it and vividly showcases her personality.
Integrating metabolic expenditure information from wearable fitness sensors into an AI-augmented automated insulin delivery system: a randomised clinical trial
Authors: Peter G Jacobs, Navid Resalat, Wade Hilts, Gavin M Young, Joseph Leitschuh, Joseph Pinsonault, Joseph El Youssef, Deborah Branigan, Virginia Gabo, Jae Eom, Katrina Ramsey, Robert Dodier, Clara Mosquera-Lopez, Leah M Wilson, Jessica R Castle
Journal: The Lancet Digital Health (2023)

Exercise can rapidly drop glucose in people with type 1 diabetes. Ubiquitous wearable fitness sensors are not integrated into automated insulin delivery (AID) systems. We hypothesised that an AID can automate insulin adjustments using real-time wearable fitness data to reduce hypoglycaemia during exercise and free-living conditions compared with an AID not automating use of fitness data.
Harnessing wearables and mobile phones to improve glycemic outcomes with automated insulin delivery
Authors: Dana M Lewis
Journal: The Lancet Digital Health (2023)

There is increasing interest in incorporating wearable and mobile phone data, including heart rate and accelerometer data, into automated insulin delivery (AID) systems to improve glucose outcomes and reduce burden on people living with diabetes. A challenge with any type of insulin delivery system is that once insulin is delivered, it cannot be removed from the body, and so improved ability to adjust and reduce insulin concentration in advance of or in response to physical activity is one area of opportunity for improving outcomes.
Safety, tolerability, and immunogenicity of the Ebola Sudan chimpanzee adenovirus vector vaccine (cAd3-EBO S) in healthy Ugandan adults: a phase 1, open-label, dose-escalation clinical trial
Authors: Betty Mwesigwa, Katherine V Houser, Amelia R Hofstetter, Ana M Ortega-Villa, Prossy Naluyima, Francis Kiweewa, Immaculate Nakabuye, Galina V Yamshchikov, Charla Andrews, Mark O'Callahan, Larisa Strom, Steven Schech, Leigh Anne Eller, Erica L Sondergaard, Paul T Scott, Mihret F Amare, Kayvon Modjarrad, Amir Wamala, Allan Tindikahwa, Ezra Musingye, Jauhara Nanyondo, Martin R Gaudinski, Ingelise J Gordon, LaSonji A Holman, Jamie G Saunders, Pamela J M Costner, Floreliz H Mendoza, Myra Happe, Patricia Morgan, Sarah H Plummer, Somia P Hickman, Sandra Vazquez, Tamar Murray, Jamilet Cordon, Caitlyn N M Dulan, Ruth Hunegnaw, Manjula Basappa, Marcelino Padilla, Suprabhath R Gajjala, Phillip A Swanson, Bob C Lin, Emily E Coates, Jason G Gall, Adrian B McDermott, Richard A Koup, John R Mascola, Aurélie Ploquin, Nancy J Sullivan, Hannah Kibuuka, Julie A Ake, Julie E Ledgerwood, Jaqueline Namugabo, Claire Beingana, Maureen G. Mukyala, Joseph Wandege, Christine Nanteza, Brenda Atwijuka, Juliet Kizanye, Gertrude Nassanga, Joanita Namuli, Herbert Kityo, Mathias Ssekitoleko, Roy Nassaka, Hilda Mutebe, Mable Kabahubya, Alicia T. Widge, Sarah E. O'Connell, Obrimpong Amoa-Awua, Sandeep R. Narpala, Britta Flach, Josephine Cox, Allison Beck, Mercy Guech, Ellie Seo, Judy A. Stein
Journal: The Lancet Infectious Diseases (2023)
Reply to Z.R. McCaw et al
Authors: Ursula A. Matulonis, Domenica Lorusso, Ana Oaknin, Sandro Pignata, Andrew Dean, Hannelore Denys, Nicoletta Colombo, Toon Van Gorp, Jason A. Konner, Margarita Romeo Marin, Philipp Harter, Conleth G. Murphy, Jiuzhou Wang, Elizabeth Noble, Brooke Esteves, Michael Method, Robert L. Coleman
Journal: Journal of Clinical Oncology (2023)
Residual β-Cell Function Is Associated With Longer Time in Range in Individuals With Type 1 Diabetes
Authors: Coco M. Fuhri Snethlage, Timothy J. McDonald, Richard D. Oram, Pleun de Groen, Elena Rampanelli, Alinda W.M. Schimmel, Frits Holleman, Sarah Siegelaar, Joost Hoekstra, Catherine B. Brouwer, Filip K. Knop, C. Bruce Verchere, Daniël H. van Raalte, Bart O. Roep, Max Nieuwdorp, Nordin M.J. Hanssen
Journal: Diabetes Care (2023)

OBJECTIVE Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). We investigated the associations between residual β-cell function and metrics of continuous glucose monitoring (CGM) in individuals with T1D. RESEARCH DESIGN AND METHODS In this cross-sectional cohort comprising 489 individuals (64% female, age 41.0 ± 14.0 years), T1D duration was 15.0 (interquartile range [IQR] 6.0–29.0) years. Individuals had a time in range (TIR) of 66% (IQR 52–80%) and a urinary C-peptide-to-creatinine ratio (UCPCR) of 0.01 (IQR 0.00–0.41) nmol/mmol. To assess β-cell function, we measured UCPCR (detectable &amp;gt;0.01 nmol/mmol), and to assess α-cell function, fasting plasma glucagon/glucose ratios were measured. CGM was used to record TIR (3.9–10 mmol/L), time below range (TBR) (&amp;lt;3.9 mmol/L), time above range (TAR) (&amp;gt;10 mmol/L), and glucose coefficient of variance (CV). For CGM, 74.7% used FreeStyle Libre 2, 13.8% Medtronic Guardian, and 11.5% Dexcom G6 as their device. RESULTS The percentage of patients with T1D who had a detectable UCPCR was 49.4%. A higher UCPCR correlated with higher TIR (r = 0.330, P &amp;lt; 0.05), lower TBR (r = −0.237, P &amp;lt; 0.05), lower TAR (r = −0.302, P &amp;lt; 0.05), and lower glucose CV (r = −0.356, P &amp;lt; 0.05). A higher UCPCR correlated negatively with HbA1c levels (r = −0.183, P &amp;lt; 0.05) and total daily insulin dose (r = −0.183, P &amp;lt; 0.05). Glucagon/glucose ratios correlated with longer TIR (r = 0.234, P &amp;lt; 0.05). CONCLUSIONS Significantly longer TIR, shorter TBR and TAR, and lower CV were observed in individuals with greater UCPCR-assessed β-cell function. Therefore, better CGM-derived metrics in individuals with preserved β-cell function may be a contributor to a lower risk of developing long-term complications.
Cause-specific mortality by county, race, and ethnicity in the USA, 2000–19: a systematic analysis of health disparities
Authors: Laura Dwyer-Lindgren, Parkes Kendrick, Yekaterina O Kelly, Mathew M Baumann, Kelly Compton, Brigette F Blacker, Farah Daoud, Zhuochen Li, Farah Mouhanna, Hasan Nassereldine, Chris Schmidt, Dillon O Sylte, Simon I Hay, George A Mensah, Anna M Nápoles, Eliseo J Pérez-Stable, Christopher J L Murray, Ali H Mokdad
Journal: The Lancet (2023)
Table of Contents
Authors: John Taormina, D Ross Camidge, Steven Lin, Muhammad Islam, Masuma Siddiqua, Rashedul Islam, Anwar Hossain, Salman Bashar, Al Ayub, Beauty Saha, Nazrina Khatun, Nazmul Karim, Gregory Videtic, Ruth Norris, Rosie Dew, Alastair Greystoke, Adam Todd, Linda Sharp, Chao Cheng, Wei Hong, Yafang Li, Xiangjun Xiao, James Mckay, Younghun Han, Jinyoung Byun, Bo Peng, Demetrios Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig Bojesen, Maria Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David Christiani, Gad Rennert, Susanne Arnold, Gary Goodman, John Field, Michael Davies, Sanjay Shete
Journal: Journal of Thoracic Oncology (2023)
Dysthyroidism during immune checkpoint inhibitors is associated with improved overall survival in adult cancers: data mining of 1385 electronic patient records
Authors: Mathilde Beaufils, Vincent Amodru, Manuel Tejeda, Jean Marie Boher, Christophe Zemmour, Brice Chanez, Anne Sophie Chrétien, Laurent Gorvel, Gwenaelle Gravis, Damien Bruyat, Roxane Mari, Anne Madroszyk, Thomas Cuny, Anthony Gonçalves, Aaron E Lisberg, Daniel Olive, Louis Tassy, Frederic Castinetti, Philippe Rochigneux
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Dysthyroidism (DT) is a common toxicity of immune checkpoint inhibitors (ICIs) and prior work suggests that dysthyroidism (DT) might be associated with ICI efficacy. Patients and methods ConSoRe, a new generation data mining solution, was used in this retrospective study, to extract data from electronic patient records of adult cancer patients treated with ICI at Institut Paoli-Calmettes (Marseille, France). Every DT was verified and only ICI-induced DT was retained. Survival analyses were performed by Kaplan-Meier method (log-rank test) and Cox model. To account for immortal time bias, a conditional landmark analysis was performed (2 months and 6 months), together with a time-varying Cox model. Results Data extraction identified 1385 patients treated with ICI between 2011 and 2021. DT was associated with improved overall survival (OS) (HR 0.46, (95% CI 0.33 to 0.65), p&lt;0.001), with a median OS of 35.3 months in DT group vs 15.4 months in non-DT group (NDT). Survival impact of DT was consistent using a 6-month landmark analysis with a median OS of 36.7 months (95% CI 29.4 to not reported) in the DT group vs 25.5 months (95% CI 22.8 to 27.8) in the NDT group. In multivariate analysis, DT was independently associated with improved OS (HR 0.49, 95% CI 0.35 to 0.69, p=0.001). After adjustment in time-varying Cox model, this association remained significant (adjusted HR 0.64, 95% CI 0.45 to 0.90, p=0.010). Moreover, patients with DT and additional immune-related adverse event had increased OS compared with patients with isolated DT, with median OS of 38.8 months vs 21.4 months, respectively. Conclusion Data mining identified a large number of patients with ICI-induced DT, which was associated with improved OS accounting for immortal time bias.